The 100 most-cited articles in COVID-19: a bibliometric analysis.

Corona virus disease 2019 (COVID-19) pandemic, sparked by the emergence of a novel coronavirus in early 2020, has prompted a surge in published articles. This study aims to systematically analyse the characteristics and trends of impactful research in the field. The 100 most-cited publications associated with COVID-19 were identified by two independent reviewers using the 'Web of Science' database across all available journals up to the year 2023. Data collected include country, citation count, subject, level of evidence (using Oxford Centre for Evidence-Based Medicine System 2011), impact factor, funding, and study design. We identified 394 038 publications, and the 100 most-cited publications were ranked. These were cited by a total of 283 034 articles (median citation = 767), median impact factor of 66.9 and 72 articles with fundings. China (n = 44), USA (n = 19), and UK (n = 13) were the three highest contributors (n = 220 505). Most articles were level 5 evidence (n = 48), followed by level 3 (n = 28), 4 (n = 14), 2 (n = 7), and 1 (n = 3). The main subjects were mechanism of action and structures of SARS-CoV-2 virus (n = 18) and impact of COVID-19 on public health (n = 18). Publications in 2022 and 2023 predominantly focused on the impact of COVID-19. Majority of the highly cited studies were of low-to-moderate quality, with only 10 consisting of randomized controlled trials or systematic reviews with or without meta-analysis. These findings reflect a growing interest in understanding the impact of COVID-19 pandemic on public and mental health. This analysis found the potential for future double-blinded randomized controlled trials to validate existing findings.

Preclinical Evaluation of the FGFR-Family Inhibitor Futibatinib for Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite decades of clinical trials, the overall survival rate for patients with relapsed and metastatic disease remains below 30%, underscoring the need for novel treatments. FGFR4, a receptor tyrosine kinase that is overexpressed in RMS and mutationally activated in 10% of cases, is a promising target for treatment. Here, we show that futibatinib, an irreversible pan-FGFR inhibitor, inhibits the growth of RMS cell lines in vitro by inhibiting phosphorylation of FGFR4 and its downstream targets. Moreover, we provide evidence that the combination of futibatinib with currently used chemotherapies such as irinotecan and vincristine has a synergistic effect against RMS in vitro. However, in RMS xenograft models, futibatinib monotherapy and combination treatment have limited efficacy in delaying tumor growth and prolonging survival. Moreover, limited efficacy is only observed in a PAX3-FOXO1 fusion-negative (FN) RMS cell line with mutationally activated FGFR4, whereas little or no efficacy is observed in PAX3-FOXO1 fusion-positive (FP) RMS cell lines with FGFR4 overexpression. Alternative treatment modalities such as combining futibatinib with other kinase inhibitors or targeting FGFR4 with CAR T cells or antibody-drug conjugate may be more effective than the approaches tested in this study.

The secretory phenotypes of envenomed cells: Insights into venom cytotoxicity.

Snake envenomation is listed as Category A Neglected Tropical Diseases (NTD) by World Health Organization, indicates a severe public health problem. The global figures for envenomation cases are estimated to be more than 1.8 million annually. Even if the affected victims survive the envenomation, they might suffer from permanent morbidity due to local envenomation. One of the most prominent local envenomation is dermonecrosis. Dermonecrosis is a pathophysiological outcome of envenomation that often causes disability in the victims due to surgical amputations, deformities, contracture, and chronic ulceration. The key venom toxins associated with this local symptom are mainly attributed to substantial levels of enzymatic and non-enzymatic toxins as well as their possible synergistic actions. Despite so, the severity of the local tissue damage is based on macroscopic observation of the bite areas. Furthermore, limited knowledge is known about the key biomarkers involved in the pathogenesis of dermonecrosis. The current immunotherapy with antivenom is also ineffective against dermonecrosis. These local effects eventually end up as sequelae. There is also a global shortage of toxins-targeted therapeutics attributed to inadequate knowledge of the actual molecular mechanisms of cytotoxicity. This chapter discusses the characterization of secretory phenotypes of dermonecrosis as an advanced tool to indicate its severity and pathogenesis in envenomation. Altogether, the secretory phenotypes of envenomed cells and tissues represent the precise characteristics of dermonecrosis caused by venom toxins.

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease.

BACKGROUND: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. OBJECTIVES: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. METHODS: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. RESULTS: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010). CONCLUSIONS: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

[Hongjing-1 Recipe maintains the expression level of Connexin43 in the penile tissue of SD rats with bilateral cavernous nerve injury].

OBJECTIVE: To explore the effects of Hongjing-1 Recipe (HJ-1) on erectile function and the expression of the gap junction protein Connexin43 (Cx43) in the penile tissue in male rats with bilateral cavernous nerve injury (BCNI). METHODS: Fifty male SD rats were randomly divided into five groups of an equal number: sham operation, BCNI model control, and low-, medium- and high-dose HJ-1. The BCNI model was made in the latter four groups by clamping the bilateral cavernous nerves with hemostatic forceps. Three days after modeling, the rats in the sham operation and BCNI model control groups were treated intragastrically with pure water and those in the low-, medium- and high-dose HJ-1 groups with HJ-1 at 2.835, 5.67 and 11.34 g/kg/d, respectively, all for 28 successive days. Then, the animals were subjected to intracavernous pressure (ICP) measurement for evaluation of their erectile function and immunofluorescence staining and Western blot for determination of the Cx43 level in the penile tissue. RESULTS: The BCNI model controls, compared with the rats in the sham operation group, showed a dramatically decreased ratio of maximum ICP to mean arterial pressure (mICP/MAP) (0.40 ± 0.04 vs 0.83 ± 0.10, P < 0.01) and that of total ICP to MAP (tICP/MAP) (21.89 ± 2.16 vs 50.27 ± 4.45, P < 0.01), as well as a down-regulated expression of Cx43 in the penile tissue (P < 0.01). In comparison with the rats in the BCNI model control group, those in the medium- and high-dose HJ-1 groups exhibited significantly increased ratios of mICP/MAP (0.54 ± 0.05, P < 0.05; 0.61 ± 0.06, P < 0.01) and tICP/MAP (31.20 ± 3.85, P < 0.01; 37.82 ± 4.17, P < 0.01) and up-regulated expression of Cx43 (P<0.05 and P<0.01). CONCLUSIONS: Hongjing-1 Recipe can effectively improve ED in rats with bilateral cavernous nerve injury, which may be attributed to its effect of maintaining the expression level of the gap junction protein Cx43 in the penile tissue.

Identification of reproduction-related genes and pathways in the Culter alburnus H-P-G axis and characterization of their expression differences in malformed and normal gynogenetic ovaries.

This study applied RNA-seq technology to discover reproduction-related genes and pathways in female topmouth culter brain (including pituitary) and ovarian tissues. In functional analysis, 2479 and 2605 unigenes in the brain and ovary tissue were assigned to the "reproductive process" subcategory in addition to the 2660 and 2845 unigenes assigned to the "reproduction" subcategory. Twenty-three complete cDNA sequences were identified through the different gene expression (DGE) approach from five reproduction-related pathways (MAPK signaling pathway, neuroactive ligand-receptor interaction pathway, gonadotropin-releasing hormone signaling pathway, oocyte meiosis pathway, and steroid biosynthesis pathway). The expression levels of 16 candidate genes using qPCR in this study were in accordance with the results of transcriptome analysis. In addition, the expression levels of the FSH, 3ß-HSD, PGR, and NPYR genes in malformed gynogenetic ovaries were considerably low, which was consistent with the progress of oocytogenesis in the ovaries of topmouth culter. The high expression of these four genes in the ovaries of normal topmouth culter suggested they might involve in the preparation for the shift of oogenesis to ovulation. Hence, our work identified a set of annotated gene products that are candidate factors affecting reproduction in the topmouth culter H-P-G axis. These results could be essential for further research in functional genomics and genetic editing for topmouth culter reproduction.

[Covered airway stent loaded with (125)I seeds for tracheal adenoid cystic carcinoma: a clinical observation of 8 cases].

Objective: To explore the efficacy and safety of the covered airway stent loaded with (125)I seeds for the treatment of tracheal adenoid cystic carcinoma (TACC). Methods: We retrospectively reviewed the clinical data from 8 patients with TACC who had received placement of the covered stent loaded with (125)I seeds between December 2014 and July 2017 in the endoscopic center of the Second Affiliated Hospital of Xiamen Medical College. We compared the difference in the dyspnea index, the diameter of the airway lumen, and the lesion surrounding the airway wall before and after treatment. The complications were also recorded during follow-up. Results: Eight patients underwent successful placement of a total of 11 radioactive stents (2 straight-type stents, 2 L-shape stents, and 7 Y-shape stents, all loaded a total of 243 radioactive particles). Displacement of stents took place within 2 weeks in 2 patients, who were managed with re-stenting and fixation. No further displacement occurred during follow-up. The median time to stent removal was 2.9(interquartile range: 2.3,3.0) months. After stent placement, the dyspnea index was significantly decreased compared with pre-treatment level (mean: 0.1 vs. 3.4, t=8.881, P<0.001). Bronchoscopic re-assessment showed that the residual tumor within the airway was detected in only one patient and that the tumor completely disappeared in the remaining 7 patients. Treatment with stents loaded with radioactive particles yielded smooth and pale airway mucosa with formation of partial scar formation. Chest computed tomography re-assessment demonstrated significantly larger luminal diameter than that before treatment (mean: 13.1 mm vs. 3.3 mm, t=-7.839, P<0.001). The airway wall thickness was notably reduced after treatment (mean: 4.3 mm vs. 14.4 mm, t=7.620, P<0.001). The lesions surrounding the airway wall completely disappeared in 7 patients and decreased for more than 50% in a single patient. The median duration of follow-up was 28.0(interquartile range: 24.8,31.5) months. Recurrence of tumor was documented in a single case within 2 years. Six patients did not experience recurrence within the 2-year follow-up period. No death or severe complications were recorded during follow-up. Conclusion: The (125)I radioactive stent is effective for dilating the stenotic airway and ameliorating the symptoms, and thus might be an effective and safe method for the treatment of TACC. Further studies that explore the efficacy of stents loaded with (125)I particles are needed.

Low Tortuous, Highly Conductive, and High-Areal-Capacity Battery Electrodes Enabled by Through-thickness Aligned Carbon Fiber Framework.

Thick electrode with high-areal-capacity is a practical and promising strategy to increase the energy density of batteries, but development toward thick electrode is limited by the electrochemical performance, mechanical properties, and manufacturing approaches. In this work, we overcome these limitations and report an ultrathick electrode structure, called fiber-aligned thick or FAT electrode, which offers a novel electrode design and a scalable manufacturing strategy for high-areal-capacity battery electrodes. The FAT electrode uses aligned carbon fibers to construct a through-thickness fiber-aligned electrode structure with features of high electrode material loading, low tortuosity, high electrical and thermal conductivity, and good compression property. The low tortuosity of FAT electrode enables fast electrolyte infusion and rapid electron/ion transport, exhibiting a higher capacity retention and lower charge transfer resistance than conventional slurry-casted thick electrode design.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development for screening of potential tamoxifen-drug/herb interaction via in vitro cytochrome P450 inhibition assay.

Screening for potential drug-drug interaction (DDI) or herb-drug interaction (HDI) using in vitro cytochrome P450 inhibition (IVCI) assays requires robust analytical methods with high sensitivity and reproducibility. Utilization of liquid chromatography-mass spectrometry (LC-MS) for analyte quantification is often hampered by the presence of non-volatile IVCI sample buffer constituents that often results in ion suppression. In this study, to enable screening of drug interactions involving tamoxifen (TAM) metabolism using IVCI-LC-MS/MS, a liquid-liquid extraction (LLE) method was developed and optimized for sample clean-up. Utilization of chloroform as extraction solvent and adjustment of sample pH to 11 was found to result in satisfactory recovery (>70%) and low ion suppression (<19%). A LC-MS/MS method was subsequently developed and validated for simultaneous quantification of major TAM metabolites, such as N-desmethyltamoxifen (NDT), endoxifen (EDF) and 4-hydroxytamoxifen (HTF) to enable IVCI sample analysis. Satisfactory separation of E-/Z-isomers of endoxifen with peak resolution (Rs) of 1.9 was achieved. Accuracy and precision of the method was verified within the linear range of 0-50 ng/mL for NDT, 0-25 ng/mL for HTF and 0-25 ng/mL for EDF (E/Z isomers). Inhibitory potency (IC50, Ki and mode of inhibition) of known CYP inhibitors and Strobilanthes crispus extract was then evaluated using the validated method. In summary, the results demonstrated applicability of the developed LLE and validated LC-MS/MS method for in vitro screening of DDI and HDI involving TAM metabolism.

Lactococcus lactis harbouring Ara h 2.02 alleviates allergen-specific Th2-associated responses in sensitized mice.

AIM: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. METHODS AND RESULTS: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen-specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL-4, IL-13, IL-6) or increase in Th1 (IFN-γ) cytokines, both groups showed lower IL-10 level, while the IL-4 : IFN-γ ratio was significantly lower for rLl compared to Ll group. CONCLUSIONS: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2-associated responses in allergen-challenged mice and a possible added allergen-specific prophylactic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine.

Aberrant activation of Wnt signaling pathway altered osteocyte mineralization.

Mineralization of bone is a dynamic process, involving a complex interplay between cells, secreted macromolecules, signaling pathways, and enzymatic reactions; the dysregulation of bone mineralization may lead to serious skeletal disorders, including hypophosphatemic rickets, osteoporosis, and rheumatoid arthritis. Very few studies have reported the role of osteocytes - the most abundant bone cells in the skeletal system and the major orchestrators of bone remodeling in bone mineralization, which is owed to their nature of being deeply embedded in the mineralized bone matrix. The Wnt/ß-catenin signaling pathway is actively involved in various life processes including osteogenesis; however, the role of Wnt/ß-catenin signaling in the terminal mineralization of bone, especially in the regulation of osteocytes, is largely unknown. This research demonstrates that during the terminal mineralization process, the Wnt/ß-catenin pathway is downregulated, and when Wnt/ß-catenin signaling is activated in osteocytes, dendrite development is suppressed and the expression of dentin matrix protein 1 (DMP1) is inhibited. Aberrant activation of Wnt/ß-catenin signaling in osteocytes leads to the spontaneous deposition of extra-large mineralized nodules on the surface of collagen fibrils. The altered mineral crystal structure and decreased bonding force between minerals and the organic matrix indicate the inferior integration of minerals and collagen. In conclusion, Wnt/ß-catenin signaling plays a critical role in the terminal differentiation of osteocytes and as such, targeting Wnt/ß-catenin signaling in osteocytes may serve as a potential therapeutic approach for the management of bone-related diseases.

Cloning, overexpression, purification, and modeling of a lectin (Rhinocelectin) with antiproliferative activity from Tiger Milk Mushroom, Lignosus rhinocerus.

A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with a predicted molecular mass of 22.8 kDa, was overexpressed in water-soluble form without signal peptide and purified via native affinity chromatography Ni-NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin-related plant lectin. In its native form, Rhinocelectin exists as a homo-tetramer predicted with four chains of identical proteins consisting of 11 beta-sheet structures with only one alpha-helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA-MB-231 and breast cancer MCF-7 are 36.52 ± 13.55 µg mL-1 and 53.11 ± 22.30 µg mL-1 , respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 µg mL-1 . The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 µg mL-1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 µg mL-1 . The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 µg mL-1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 µg mL-1 and 6.250 µg mL-1 , respectively.

[Application of dental floss traction-assisted endoscopic submucosa dissection to rectal neuroendocrine neoplasm].

Objective: To evaluate the safety and efficacy of dental floss traction-assisted endoscopic submucosal dissection (DFS-ESD) for rectal neuroendocrine neoplasm (NEN). Methods: A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital, Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled, including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1, and the mean size was 0.8±0.2(0.5-1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS-ESD treatment (DFS-ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS-ESD group, after the mucosa was partly incised along the marker dots, the endoscopy was extracted, and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted, the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time, modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS-ESD group), en bloc resection rate, R0 resection rate, morbidity of operative complication, recurrence and metastasis were compared between two groups. Results: The average tumor size was (0.8±0.2) cm in DFS-ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425, P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm, 13 were G1 and 4 were G2 in DFS-ESD group, while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative, the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS-ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS-ESD group (t=1.776, P=0.084). The modified operation time of DFS-ESD group was (11.9±2.8) minutes, which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3±0.6) days and (2.0±0.5) days in conventional ESD group and DFS-ESD group, respectively, without significant difference (t=1.436, P=0.160). No patient was transferred to surgery, and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor-related death, and all the patients recovered well during a follow-up period of 14(1-24) months. Conclusion: Dental floss traction-assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Biofilm inhibiting activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms.

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.

Interhospital Transfer of Children in Septic Shock: A Clinician Interview Qualitative Study.

OBJECTIVE:: To determine the factors that influence the decision to transfer children in septic shock from level II to level I pediatric intensive care unit (PICU) care. DESIGN:: Interviews with level II PICU physicians in Michigan and Northwest Ohio. A hypothetical scenario of a 14-year-old boy in septic shock was presented. BASELINE:: 40 mL/kg fluid resuscitation, central venous and peripheral arterial access, and high-dose vasopressor infusions were provided. ESCALATION POINT:: After 2 hours. When the patient is in catecholamine-resistant shock and oliguric, invasive mechanical ventilation is initiated. MEASUREMENTS AND MAIN RESULTS:: All 19 eligible physicians participated. At baseline, respondents would assess measures of perfusion and hemodynamics: blood pressure (BP; 15 [79%]), lactate (12 [63%]), and central venous oxygen saturation (ScvO2; 10 [53%]). Poor clinical response was signified by low BP (11 [58%]), elevated lactate (9 [47%]), low urine output (8 [42%]), and low ScvO2 (6 [32%]). At the escalation point, 13 of 18 respondents felt there was <50% probability of clinical turnaround without escalating treatment, though only 3 (16%) would call to discuss transfer. Seven (37%) respondents would give more fluid, whereas 8 (42%) would use central venous pressure to guide fluid resuscitation. Ultimately, 15 (79%) respondents would transfer for extracorporeal membrane oxygenation (ECMO) or renal replacement therapy if there was no response to escalated care. Four (21%) respondents would not transfer the patient: 1 felt appropriate care could be provided in the level II PICU, 2 felt transfer was unconventional, and 1 was unaware ECMO could be provided in refractory septic shock. CONCLUSIONS:: Level II to level I PICU transfer of children with septic shock is triggered by perceived nonresponse to locally available therapies. Few referring physicians do not transfer children in refractory septic shock. This study provides new insight into decision-making that influences the interhospital transfer of children with septic shock.

Incorporation of hydroxyproline in bacterial collagen from Streptococcus pyogenes.

Bacterial collagen-like proteins differ from vertebrate collagens in that they do not contain hydroxyproline, which is seen as a characteristic of the vertebrate collagens, and which provides a significant contribution to the stability of the collagen triple-helix at body temperature. Despite this difference, the bacterial collagens are stable at around body temperature through inclusion of other stabilising sequence elements. Another difference is the lack of aggregation, and certain vertebrate collagen binding domains that can be introduced into the bacterial sequence lack full function when hydroxyproline is absent. In the present study we have demonstrated that a simple method utilising co-translational incorporation during fermentation can be used to incorporate hydroxyproline into the recombinant bacterial collagen. The presence and amount of hydroxyproline incorporation was shown by amino acid analysis and by mass spectrometry. A small increase in thermal stability was observed using circular dichroism spectroscopy. STATEMENT OF SIGNIFICANCE: Recombinant bacterial collagens provide a new opportunity for biomedical materials as they are readily produced in large quantity in E. coli. Unlike animal collagens, they are stable without the need for inclusion of a secondary modification system for hydroxyproline incorporation. In animal collagens, however, introduction of hydroxyproline is essential for stability and is also important for functional molecular interactions within the mammalian extracellular matrix. The present study has shown that hydroxyproline can be readily introduced into recombinant S. pyogenes bacterial collagen through direct co-translational incorporation of this modified imino acid during expression using the codons for proline in the introduced gene construct. This hydroxylation further improves the stability of the collagen and is available to enhance any introduced molecular functions.

The Therapeutic Potential of Hyaluronan in COPD.

Insights into the clinical course of COPD indicate the need for new therapies for this condition. The discovery of alpha-1 antitrypsin deficiency (AATD) led to the protease-antiprotease imbalance hypothesis, which was applied to COPD related to AATD as well as COPD not related to AATD. The discovery of AATD brought recognition to the importance of elastin fibers in maintaining lung matrix structure. Two cross-linking amino acids, desmosine and isodesmosine (DI), are unique to mature elastin and can serve as biomarkers of the degradation of elastin. The intravenous augmentation treatment and lung density in severe alpha-1 antitrypsin deficiency (RAPID) study shows a correlation of an anatomic index of COPD (on CT imaging) correlating with a chemical indicator of matrix injury in COPD, DI. The results suggest that preservation of lung elastin structure may slow the progression of COPD. Hyaluronan aerosol decreases the severity of elastase-induced emphysema in animals and has induced reductions in DI levels in preliminary human studies. Hyaluronan deserves further development as a therapy for COPD.

Spatiotemporal variations and relationship of PM and gaseous pollutants based on gray correlation analysis.

The present work characterizes the spatiotemporal variations of air pollution at four sites in Xi'an city. The investigations lasted for 1 year: January 1 through December 31, 2015. The concentrations of CO, NO2, O3, PM and SO2 were systematically monitored. The gray correlation analysis was used to correlate PM2.5 and gaseous pollutants. The formation mechanisms of sulfate and nitrate aerosols were discussed. Results clearly revealed severe air pollution by PM2.5, PM10 and NO2 at all four sites. Significant monthly variations were observed for PM2.5, PM10, SO2 and CO with the maximum values in December/January and minimum values in June/July. The O3 level showed an opposite trend. Spatially, high variations were observed for PM and some gaseous pollutants at individual sites. Gray correlation analysis revealed the significance of various major influencing factors on seasonal PM2.5 values at each site. In general, PM10, SO2 and NO2 affect the PM2.5 more than other pollutants. For a more efficient control of air pollution, a systematic spatial characterization of the seasonal variability of individual influencing factors is necessary.

Stabilisation of Collagen Sponges by Glutaraldehyde Vapour Crosslinking.

Glutaraldehyde is a well-recognised reagent for crosslinking and stabilising collagens and other protein-based materials, including gelatine. In some cases, however, the use of solutions can disrupt the structure of the material, for example, by causing rapid dispersion or distortions from surface interactions. An alternative approach that has been explored in a number of individual cases is the use of glutaraldehyde vapour. In this study, the effectiveness of a range of different glutaraldehyde concentrations in the reservoir providing vapour, from 5% to 25% (w/v), has been explored at incubation times from 5 h to 48 h at room temperature. These data show the effectiveness of the glutaraldehyde vapour approach for crosslinking collagen and show that materials with defined, intermediate stability could be obtained, for example, to control resorption rates in vivo.

Delays in diagnosis and treatment of pulmonary tuberculosis in AFB smear-negative patients with pneumonia.

BACKGROUND: Diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (PTB). This study aimed to evaluate TB diagnostic and treatment delays in acid-fast bacilli (AFB) smear-negative patients. METHODS: This was a retrospective observational study. Patients with positive AFB culture of Mycobacterium tuberculosis complex (MTC) were selected from among hospitalised patients with a diagnosis of pneumonia. Admission ward, anti-tuberculosis treatment and the duration of AFB culture were compared between smear-positive and smear-negative patients. RESULTS: Of the 70 patients with positive isolation of MTC in AFB culture, 27 (38.5%) were smear-negative; of these, 18 (66.7%) were not isolated while in hospital, and 17 (63%) were neither diagnosed nor treated for TB. In contrast, 41 of the 43 smear-positive patients (95.3%) were directly admitted or quickly transferred to the isolation room and started on anti-tuberculosis treatment (P < 0.001). Samples from smear-negative patients required more time to grow MTC in AFB culture than those of smear-positive patients (23 days vs. 14 days, P < 0.001). Diabetes was significantly associated with AFB smear positivity, with an odds ratio of 12.2. CONCLUSIONS: Negative AFB smears caused significant diagnostic and treatment delay. Patients staying in the general ward were exposed to TB patients who were not diagnosed in time.